Mediator of DNA damage checkpoint 1 (MDC1) regulates mitotic progression.
Human mediator of DNA damage checkpoint 1 (hMDC1) is an essential component of the cellular response to DNA double strand breaks. Recently, hMDC1 has been shown to associate with a subunit of the anaphase-promoting complex/cyclosome (APC/C) (Coster, G., Hayouka, Z., Argaman, L., Strauss, C., Friedle...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1797089053479272448 |
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| author | Townsend, K Mason, H Blackford, A Miller, E Chapman, R Sedgwick, G Barone, G Turnell, A Stewart, G |
| author_facet | Townsend, K Mason, H Blackford, A Miller, E Chapman, R Sedgwick, G Barone, G Turnell, A Stewart, G |
| author_sort | Townsend, K |
| collection | OXFORD |
| description | Human mediator of DNA damage checkpoint 1 (hMDC1) is an essential component of the cellular response to DNA double strand breaks. Recently, hMDC1 has been shown to associate with a subunit of the anaphase-promoting complex/cyclosome (APC/C) (Coster, G., Hayouka, Z., Argaman, L., Strauss, C., Friedler, A., Brandeis, M., and Goldberg, M. (2007) J. Biol. Chem. 282, 32053-32064), a key regulator of mitosis, suggesting a possible role for hMDC1 in controlling normal cell cycle progression. Here, we extend this work to show that hMDC1 regulates normal metaphase-to-anaphase transition through its ability to bind directly to the APC/C and modulate its E3 ubiquitin ligase activity. In support of a role for hMDC1 in controlling mitotic progression, depletion of hMDC1 by small interfering RNA results in a metaphase arrest that appears to be independent of both BubR1-dependent signaling pathways and ATM/ATR activation. Mitotic cells lacking hMDC1 exhibit markedly reduced levels of APC/C activity characterized by reduced levels of Cdc20, and a failure of Cdc20 to bind the APC/C and CREB-binding protein. We suggest therefore that hMDC1 functionally regulates the normal metaphase-to-anaphase transition by modulating the Cdc20-dependent activation of the APC/C. |
| first_indexed | 2024-03-07T02:58:57Z |
| format | Journal article |
| id | oxford-uuid:b04a88fc-c520-456b-9cdd-df0ca45a9238 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:58:57Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:b04a88fc-c520-456b-9cdd-df0ca45a92382022-03-27T03:55:20ZMediator of DNA damage checkpoint 1 (MDC1) regulates mitotic progression.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b04a88fc-c520-456b-9cdd-df0ca45a9238EnglishSymplectic Elements at Oxford2009Townsend, KMason, HBlackford, AMiller, EChapman, RSedgwick, GBarone, GTurnell, AStewart, GHuman mediator of DNA damage checkpoint 1 (hMDC1) is an essential component of the cellular response to DNA double strand breaks. Recently, hMDC1 has been shown to associate with a subunit of the anaphase-promoting complex/cyclosome (APC/C) (Coster, G., Hayouka, Z., Argaman, L., Strauss, C., Friedler, A., Brandeis, M., and Goldberg, M. (2007) J. Biol. Chem. 282, 32053-32064), a key regulator of mitosis, suggesting a possible role for hMDC1 in controlling normal cell cycle progression. Here, we extend this work to show that hMDC1 regulates normal metaphase-to-anaphase transition through its ability to bind directly to the APC/C and modulate its E3 ubiquitin ligase activity. In support of a role for hMDC1 in controlling mitotic progression, depletion of hMDC1 by small interfering RNA results in a metaphase arrest that appears to be independent of both BubR1-dependent signaling pathways and ATM/ATR activation. Mitotic cells lacking hMDC1 exhibit markedly reduced levels of APC/C activity characterized by reduced levels of Cdc20, and a failure of Cdc20 to bind the APC/C and CREB-binding protein. We suggest therefore that hMDC1 functionally regulates the normal metaphase-to-anaphase transition by modulating the Cdc20-dependent activation of the APC/C. |
| spellingShingle | Townsend, K Mason, H Blackford, A Miller, E Chapman, R Sedgwick, G Barone, G Turnell, A Stewart, G Mediator of DNA damage checkpoint 1 (MDC1) regulates mitotic progression. |
| title | Mediator of DNA damage checkpoint 1 (MDC1) regulates mitotic progression. |
| title_full | Mediator of DNA damage checkpoint 1 (MDC1) regulates mitotic progression. |
| title_fullStr | Mediator of DNA damage checkpoint 1 (MDC1) regulates mitotic progression. |
| title_full_unstemmed | Mediator of DNA damage checkpoint 1 (MDC1) regulates mitotic progression. |
| title_short | Mediator of DNA damage checkpoint 1 (MDC1) regulates mitotic progression. |
| title_sort | mediator of dna damage checkpoint 1 mdc1 regulates mitotic progression |
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